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Projects / Programmes source: ARIS

Biomarkers of endometriosis: transcriptomics and proteomics approach

Research activity

Code Science Field Subfield
3.05.00  Medical sciences  Human reproduction   

Code Science Field
B000  Biomedical sciences   

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
Keywords
biomarkers, transcriptome, proteome, protein arrays, micro RNA
Evaluation (rules)
source: COBISS
Researchers (13)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  55378  PhD Jerzy Adamski  Biochemistry and molecular biology  Researcher  2021 - 2022  415 
2.  21364  PhD Helena Ban Frangež  Human reproduction  Researcher  2022  194 
3.  53995  Eva Hafner  Metabolic and hormonal disorders  Researcher  2021 - 2022  22 
4.  53964  PhD Teja Klančič  Metabolic and hormonal disorders  Researcher  2019 - 2020  24 
5.  38540  Špela Kos    Researcher  2019 - 2022 
6.  11699  PhD Tea Lanišnik Rižner  Metabolic and hormonal disorders  Head  2019 - 2022  574 
7.  37853  Tatjana Lončar    Technical associate  2019 - 2022 
8.  10691  PhD Joško Osredkar  Human reproduction  Researcher  2019 - 2022  1,308 
9.  55051  PhD Maja Pušić Novak  Human reproduction  Researcher  2020 - 2022  51 
10.  22459  PhD Tadeja Režen  Neurobiology  Researcher  2019 - 2022  242 
11.  35750  Vera Troha Poljančič    Technical associate  2019 - 2022 
12.  06976  PhD Andrej Vogler  Human reproduction  Researcher  2019 - 2021  319 
13.  39126  PhD Alja Zottel  Biochemistry and molecular biology  Researcher  2022  62 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,417 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,726 
Abstract
Endometriosis is a female reproductive disorder, characterized by the presence of endometrial tissue outside the uterine cavity. It affects an estimated 176 million women worldwide and is more frequent than cancer and diabetes. The estimated prevalence is 6–10% in reproductive age women and 30%–50% in women with infertility and/or pain. Endometriosis is associated with disturbed immune system, aberrant apoptosis, cell adhesion, degradation of extracellular matrix, angiogenesis, cell communication and other pathological processes. The symptoms of endometriosis are non-specific and include debilitating pain and infertility. The gold standard for diagnosis of endometriosis is still laparoscopy, a surgical visual inspection of the pelvic organs. As a result of these non-specific symptoms and surgical diagnosis, there is an average delay of 6.7 years between the onset of symptoms and the diagnosis. At present there are no biomarkers for non-invasive diagnosis of endometriosis, although different approaches have already been used in the search for blood biomarkers. Early research focused mainly on individual proteins, while in the last decades also omics approaches have been introduced into biomarker discovery. Changes in micro RNA and protein profiles have been reported in endometriotic lesions and this can be reflected in blood of these patients. We hypothesize that biomarkers for non-invasive diagnostics of endometriosis can be identified in plasma samples with the transcriptomics and proteomics approaches. Our aims are: 1) to identify panels of micro RNAs and proteins specific for patients with endometriosis and 2) to develop diagnostic algorithms for clinical validation and application. These aims will be achieved by the state-of-the-art transcriptomics and proteomics approaches using miRNA and antibody arrays in the discovery phase and low density miRNA arrays and multiplex immunological assays (Luminex®) in the validation phase. The unique aspect of the proposal is evaluation of ) 2 500 miRNAs and 900 proteins in ~400 plasma samples from patients with and without endometriosis and development of diagnostic algorithms based on combination of proteomic, metabolomic and clinical data. Our case-control study will include patients with endometriosis like symptoms, stratified into case and control groups based on the laparoscopic and histological findings. The targeted transcriptomics and proteomics study will comprise discovery phase to identify new miRNAs and proteins associated with endometriosis on a smaller number of samples and the validation phase where we aim to determine concentrations of these miRNAs and proteins on all case and control samples. Diagnostic algorithms will be constructed using sound bioinformatics and multivariate statistics. The proposed project will identify novel miRNA molecules and proteins associated with endometriosis and will pinpoint the disturbed molecular processes. The project may thus indirectly contribute to earlier treatment and concurrently decreased infertility and may also advance understanding of pathophysiology of this intriguing disease, which may in a long term lead to development of new options for treatment. The study will be performed in collaboration with Department of Gynaecology, University Medical Centre Ljubljana, Centre for Functional Genomics and Biochips at the Faculty of Medicine, Medical University Vienna, Austria and University of Tartu, Estonia.
Significance for science
While the classical proteomics approach certainly has a relevant role in the search of potential serum/plasma/urine biomarkers of endometriosis, it has limitations as well and biomarkers identified with this technology are still far from clinical application. Our study using antibody arrays represents a novel approach that has not yet been explored in the context of endometriosis, but was successfully employed for other diseases, e.g. hepatocellular carcinoma and interstitial lung disease. MicroRNA molecules have cruical roles in variety of physiological and pathophysiological preocesses and have also been associated with endometriosis. Our targeted transcriptomics study will therefore focus also on microRNA molecules, which act at post-transcriptional level and regulate different cellular processes. So far miRNA arrays have not been used for discovery of biomarkers of endometriosis. The aims of the project will be achieved by the state-of-the-art targeted transcriptomics and proteomics approaches. The unique aspect of the proposal is evaluation of ) 2500 miRNAs and 900 proteins in ~400 plasma samples from patients with and without endometriosis. The proposed project will identify novel miRNA molecules and proteins associated with endometriosis and will validate miRNA molecule and proteins reported previously as biomarkers of endometriosis. In this manner the project will result in diagnostic models for early detection of endometriosis, but will also pinpoint the disturbed molecular processes. The novelties of the project are as follows: 1) use of micro RNA and antibody arrays in endometriosis biomarker discovery, 2) discovery and validation phases followed by extensive and sound bioinformatics and statistical analysis, and especially 3) development of algorithm, which will include transcriptomis, proteomics and clinical data for detection of endometriosis applicable for further clinical validation. Diagnostic algorithms combining proteomic, metabolomics and clinical data have not yet been reported.  The proposed project may indirectly contribute to earlier treatment and concurrently decreased infertility, but may also advance understanding of pathophysiology of this intriguing disease, which may open new avenues in research and in a long term contribute to development of new options for treatment.
Significance for the country
While the classical proteomics approach certainly has a relevant role in the search of potential serum/plasma/urine biomarkers of endometriosis, it has limitations as well and biomarkers identified with this technology are still far from clinical application. Our study using antibody arrays represents a novel approach that has not yet been explored in the context of endometriosis, but was successfully employed for other diseases, e.g. hepatocellular carcinoma and interstitial lung disease. MicroRNA molecules have cruical roles in variety of physiological and pathophysiological preocesses and have also been associated with endometriosis. Our targeted transcriptomics study will therefore focus also on microRNA molecules, which act at post-transcriptional level and regulate different cellular processes. So far miRNA arrays have not been used for discovery of biomarkers of endometriosis. The aims of the project will be achieved by the state-of-the-art targeted transcriptomics and proteomics approaches. The unique aspect of the proposal is evaluation of ) 2500 miRNAs and 900 proteins in ~400 plasma samples from patients with and without endometriosis. The proposed project will identify novel miRNA molecules and proteins associated with endometriosis and will validate miRNA molecule and proteins reported previously as biomarkers of endometriosis. In this manner the project will result in diagnostic models for early detection of endometriosis, but will also pinpoint the disturbed molecular processes. The novelties of the project are as follows: 1) use of micro RNA and antibody arrays in endometriosis biomarker discovery, 2) discovery and validation phases followed by extensive and sound bioinformatics and statistical analysis, and especially 3) development of algorithm, which will include transcriptomis, proteomics and clinical data for detection of endometriosis applicable for further clinical validation. Diagnostic algorithms combining proteomic, metabolomics and clinical data have not yet been reported.  The proposed project may indirectly contribute to earlier treatment and concurrently decreased infertility, but may also advance understanding of pathophysiology of this intriguing disease, which may open new avenues in research and in a long term contribute to development of new options for treatment.
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